tbuckley/cabot-search huggingface dataset:
Abstract 14721: Association of Non-Surgical Weight Loss With Speckle-Tracking Strain Parameters
Authors: Vinay B Panday, Ching-hui Sia, Tan Sik Yin, William Kong, Kian-Keong Poh
Journal: Circulation (2022)

Introduction Several studies have demonstrated that surgical weight loss improves myocardial mechanics as measured by speckle-tracking imaging. The studies, however, have mostly been conducted in morbidly obese Caucasian populations with an average body mass index (BMI) of around 40 kg/m2. To our knowledge, no study has examined whether non-surgical weight loss can improve myocardial mechanics in the less morbidly obese. Hypothesis We hypothesized that non-surgical weight loss would improve strain parameters in less morbidly obese patients. Methods 66 patients were recruited. Participants underwent a 16-week lifestyle intervention (LSI) programme. LSI consisted of a) dietary interventions involving regular consultations with the dietician and meal planning and b) exercise prescription with pedometers Echocardiography with speckle tracking was performed at baseline and post-intervention. Paired analysis using paired T-test evaluating changes in weight and strain parameters were conducted after intervention. Results The primary outcome was improvement in strain parameters after weight loss. Table 1 depicts the characteristics of the participants and the change in strain parameters. Participants attained significant weight loss after LSI ( 28.2 +/- 2.66 kg/m 2 vs 25.8 +/- 2.84 kg/m 2 , p =0.001). There was a significant reduction in waist and hip circumference (90.7 +/- 7.64 cm vs 83.62 +/- 7.13 cm, p =0.01) and (103.28 +/- 2.03 cm vs 97.74 +/- 6.24 cm, p=0.01) respectively. However this was not associated with improvement in strain parameters of the left atrium (51.456 +/- 11.24 vs 48.78 +/- 19.09, p =0.190) , left ventricle (-22.05 +/- 2.98 vs 22.77 +/- 3.21, p= 0.125) and right ventricle (-21.56 +/- 3.32 vs -22.02 +/- 3.59, p = 0.404). Conclusion Non-surgical weight loss was not associated with an improvement in echocardiographic speckle-tracking strain parameters.
Abstract 14954: Mitochondrial C-Src Regulates Impaired Mitochondrial Bioenergetics in Right Ventricles in Pulmonary Hypertension
Authors: Peng Zhang, Alexander Vang, Denielli da Silva Goncalves Bos, Julia Feord, Eric Wang, Natalie D’Silva, Alexsandra Zimmer, Gaurav Choudhary
Journal: Circulation (2022)

Introduction: Pulmonary hypertension (PH) has poor prognosis with presence of right ventricular (RV) dysfunction. However, no RV targeted therapies are available. Mitochondrial (Mito) energy deficiency is detrimental on RV function in PH, but the underlying mechanism remains unclear. Tyrosine kinase phosphorylation (P-Tyr) has been a critical regulatory mechanism in mito. While mito localized c-Src is recognized as the major tyrosine kinase, little is known regarding its role in RV in PH. Hypothesis: We hypothesized that mito c-Src regulates impaired mito bioenergetics in RV in PH. Methods: PH was induced in adult Sprague-Dawley (SD) rats by injecting 20 mg/kg SU5416, followed by 3 wks of hypoxia (10% FiO 2 ) and then 4 wks of normoxia exposure. Control rats injected with vehicle were kept in normoxia. After echocardiography and hemodynamics, RV tissues were collected for mito respiration using high resolution O2K-FluoRespirometer, mito morphology using electron microscopy, and biochemical assays. Cardiomyocytes and H9c2 cells were used for in vitro mechanistic studies. Results: Compared to controls, PH rats show increased RV systolic pressure and RV dysfunction. Mito complex I-coupled oxidative phosphorylation and electron transfer capacity are significantly reduced in RV of PH rats (O 2 flux per mass: 216±21 vs. 90±19 and 209±22 vs. 91±22 pmol·s-1·mg-1, respectively, p &lt;0.01, n=6 each), which is associated with decreased ATP but no changes in mito membrane integrity, mito DNA content, or mito size. Mito c-Src kinase activity and expression are significantly reduced in RV of PH rats and in dysfunctional RV of human patients. Chemical or molecular inhibition of mito c-Src results in a similar reduction of mito respiration in culture as found in RV of PH rats and is associated with decreased ATP production. Mito c-Src phosphorylates NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2), a critical protein for complex I, and P-Tyr of NDUFV2 is reduced in RV of PH rats. Conclusions: Impaired mito bioenergetics is associated with progression of RV dysfunction. Basal mito c-Src kinase activity is required for mito bioenergetics and mito c-Src-dependent P-Tyr of NDUFV2 may serve as a regulatory mechanism in impaired RV mito bioenergetics in settings of PH.
Abstract 15084: One- versus Three-Month DAPT in Diabetic Patients With High Bleeding Risk Undergoing PCI: Results From the Xience Short DAPT Global Program
Authors: Alessandro Spirito, Roxana Mehran, Samantha Sartori, Clayton Snyder, James hermlller, Raj Makkar, Sripal Bangalore, Dominick J Angiolillo, Johny Nicolas, Junbo Ge, Birgit Vogel, Shigeru Saito, Davide Cao, Franz-Josef Neumann, Deepak Bhatt, Marco Valgimigli
Journal: Circulation (2022)

Introduction: In patients at high bleeding risk (HBR), a short dual antiplatelet therapy (DAPT) duration after coronary stenting has been associated with fewer bleeding events and preserved ischemic protection. Whether these effects are maintained in diabetic patients is unclear. Purpose: To assess the safety and efficacy of 1- versus 3-month DAPT after percutaneous coronary intervention (PCI) with stent implantation among HBR patients with or without diabetes. Methods: We included patients from three prospective, international, single-arm studies (XIENCE Short DAPT Program), which enrolled HBR patients successfully treated with a fluoropolymer-based cobalt-chromium everolimus-eluting stent (XIENCE, Abbott). Subjects were eligible for DAPT discontinuation at 1 month (XIENCE 28 USA and Global) or at 3 months (XIENCE 90), if free from ischemic events and adherent to DAPT. The primary endpoint was the composite of all-cause death or any myocardial infarction (MI). The key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding. Outcomes were assessed between 1 and 12 months after index PCI using propensity score adjustment. Results: Out of 3,352 patients, 1,299 (38.8%) had diabetes. The rate of death or MI at 12 months was higher in diabetic than in non-diabetic patients (10.1% vs 6.6%) while the rate of BARC 2-5 bleeding was similar (9.5% vs 9.2%). A one v. three months of DAPT duration resulted in a borderline reduction in death or MI (adj. HR 0.70, 95% CI 0.47-1.05) in diabetic but not in non-diabetic patients (adj. HR 1.24, 95% CI 0.86-1.79; p-interaction=0.016) and fewer BARC 2-5 bleeding in both groups (adj. HR 0.67, 95% CI 0.45-1.01 and adj. HR 0.77, 95% CI 0.56-1.06, respectively; p-interaction=0.950). Conclusions: Among HBR patients undergoing everolimus-eluting stent implantation, diabetic patients derive important benefit in reducing death and MI and bleeding events from a one month compared with three-month DAPT duration.
Abstract 14474: The Levels of Serum Insulin-Like Growth Factor Binding Protein (IGFALS) Decline Seven Days After Non-Emergent Cardiac Surgery - A Potential Link to Neuroinflammation?
Authors: Krzysztof Laudanski, Jake Karwoski, Susan Shin
Journal: Circulation (2022)

Introduction: Inflammatory response and metabolic derangements may accelerate neurodegeneration after cardiac surgery. Insulin, insulin growth factor (IGF), and insulin-like growth factor binding protein acid labile subunit (IGFALS) are the centerpieces of glucose metabolism, the critical factor determining long-term recovery from cardiac surgery and neurodegeneration progression[1]. IGFALS is a regulatory element of IGF that increases their half-life and vascular localization Hypothesis: We investigate the dynamics of IGFALS up to 3 months after cardiac surgery. We hypothesize that post-cardiac surgery IGFALS serum level abnormalities are related to changes in neuroinflammatory (BDNF, CXCL13) and neurodegeneration marker (tau). Methods: Patients (n=25) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(t baseline ), 24 hours later(t 24h ) after the first sample, 7 days(t 7d ), and 3 months(t 3m ) after t baseline . Variables regarding the surgery were collected from medical records. IGFALS levels were measured via ELISA, while neurodegeneration and neuroinflammation markers via multiplex technology. Results: Demographic variables had limited effects on IGFALS. The serum levels of IGFALS varied significantly (H[4;221]=9.146; 0.0274) (Figure 1). The serum levels were significantly lower at t 7d but recovered at t 3m . During the acute inflammatory response at t 24h IGFALS, serum levels remained unaltered. BDNF at 3m correlated with IGFALS at t 7d ( r 2 =0.38;p=0.012) and t 3m ( r 2 =0.39;p=0.018). CXCL13 demonstrated similar interactions. Tau level did not correlate with IGFALS dynamics. Conclusions: The data demonstrated a significant long-term decline in IGFALS level after cardiac surgery. The correlations suggest a potential link between IGFALS and some neuroinflammatory markers. 1. Westwood, A.J Neurology, 2014.82(18): p. 1613-9.
Abstract 15199: Automated Machine Learning (AutoML) Algorithms to Predict Post-Operative Venous Thromboembolism (VTE) Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Database
Authors: Avinash Thangirala, Yindalon Aphinyanaphongs, Ji Chen, Jacob A Martin, Usman Alam, Nehal Dhaduk, Andrew C Kelleher, Jake F Oeding, Eric Hu, Nicolai Ostberg, Gregory Katz, Shelly Brejt, Karen C Kan
Journal: Circulation (2022)

Introduction: Post-operative patients are at increased risk for venous thromboembolism (VTE). Given the morbidity and mortality associated with VTE, risk stratification calculators have been developed based on pre-operative patient characteristics. Most risk calculators rely on logistic regression (LR) analysis. However, automated machine learning (AutoML) programs consistently outperform standard LR models in non-medical contexts. This study aims to investigate the utility of novel methods in developing a model for post-operative VTE after non-cardiac and cardiac surgeries. Hypothesis: We hypothesized that AutoML models would be superior to logistic regression models in predicting post-operative VTE. Methods: We used an AutoML system developed and released by Amazon in 2020, AutoGluon v0.3.1, to predict post-operative VTE using the 2016-2018 ACS NSQIP database. A total of 3,049,617 patients and 79 pre-operative variables were included. Post-operative VTE was defined as a deep venous thrombosis (DVT) or a pulmonary embolism (PE) within 30 days of the surgery. Models were trained for four hours to optimize performance on the Brier score, with lower being better. Validation of all performance metrics was done using the 2019 ACS NSQIP database. Results: 0.79% of the patients (n = 23,974) developed post-operative VTE. Brier scores were calculated for each model with the top performing model being an ensembled neural net model having a Brier score of 0.00758 on the validation set. The corresponding AUROC and AUC-PR was 0.784 and 0.035 respectively (Figure). Conclusions: The models generated via AutoML to predict post-operative VTE had similar discriminatory characteristics to those reported in the literature. Future post-operative VTE models may benefit from AutoML analysis.
Abstract 14818: Precision Nanomedicine Targeting Novel Endothelial Mechano-Sensing Mechanisms and Treating Vascular Complications in vivo
Authors: Yun Fang
Journal: Circulation (2022)

Introduction: Endothelial mechano-transduction mechanisms are instrumental to vascular health and disease. Novel strategies targeting disease-causing mechano-sensitive pathways in dysfunctional endothelial cells could revolutionize future cardiovascular therapeutics. Vascular complications such as atherosclerosis and stenosis preferentially develop at arterial curvatures and bifurcations where endothelial cells are activated by local disturbed blood flow, leading to peripheral artery disease, carotid artery disease and ischemic stroke. Hypothesis: Current vascular therapies mainly target systematic risk factors (e.g. hypercholesterolemia and hypertension) but not the diseased vasculature, distinct molecular/cellular signatures of which can be targeted by innovated precision nanomedicine approaches. Methods: We first elucidated novel mechano-sensitive molecular mechanisms in endothelium activated by disturbed flow (DF) and then engineered rationally-designed nano-materials with purposed-constructed functionalities to deliver therapeutic nucleotides to DF-activated endothelial cells. Results: Our results elucidated previously unrecognized endothelial mechano-sensitive pathways in endothelial activation, with emphasis upon cellular metabolism (DF-induced glycolysis), human genetic variants (DF-induced suppression of PLPP3, a CAD GWAS gene), miRNA, protein stability (DF-induced NOS3 protein degradation via TXNDC5) and mRNA chemical modification/epi-transcriptome (DF-induced suppression of m7G). VCAM1-targeting nanoparticles were engineered to deliver therapeutic nucleotides such as mRNA, miRNA inhibitor, or CRISPR/Cas9 constructs specifically to inflamed endothelial cells to intervene aforementioned mechano-sensitive pathways, effectively reducing atherosclerosis and stenosis in mice. Similar approaches were very effective to promote endothelial health and lessen acute respiratory distress syndrome (ARDS) in mice induced by influenza or SARS-CoV-2 viruses. Conclusions: These results elucidate novel endothelial mechano-sensing mechanisms and provide a proof of concept of innovative targeted nanomedicine approaches, addressing an unmet medical need in vascular therapies.
Abstract 14445: Patients With Peripheral Artery Disease Living in Food Deserts Are Associated With Worse Outcomes and Suboptimal Medical Therapy
Authors: Rayan S El-Zein, Dan D Nguyen, Zhuxuan Fu, Kensey Gosch, Matthew C Bunte
Journal: Circulation (2022)

Introduction: Major adverse cardiac events (MACE) represent important clinical outcomes for patients with PAD, while also disproportionally impacting minority populations. Guideline-directed optimal medial therapy (OMT) is known to reduce MACE events, but whether the OMT-adjusted rate of MACE events are influenced by social determinants of health, including living in a food desert (FD) has not been previously explored. Methods: Patients with PAD from a single-system registry were geocoded as living in a FD vs non-FD according to the US Department of Agriculture Food Access Research Atlas. FDs are characterized as census tracts with low income and poor food access (defined as proximity to a grocery store). MACE was defined as a composite of all-cause death, acute myocardial infarction, or stroke. OMT was defined as being prescribed antiplatelet, statin, renin-angiotensin inhibitors, and with tobacco abstention. Cox proportional hazards models examined the association of area characteristics (FD, poor access, low income) and MACE, adjusted for traditional factors. Multivariable logistic regression examined the association of demographic, clinical, and area characteristics with OMT. Results: From 2015 to 2021, 1,834 (15.4%) of 11,907 lived in FDs. Patients in FDs were more likely Black or Hispanic, residing in urban areas, had low vehicle access, and had a higher prevalence of hypertension, diabetes, and chronic kidney disease. Those living in FDs had a higher adjusted risk of MACE (HR 1.17 [1.04-1.31], p=0.008) driven by all-cause death (HR 1.19 [1.03-1.37], p=0.018). Female sex, malnutrition, COPD, CKD, and low area income were significantly associated with lower odds of achieving OMT. Conclusions: Living in food deserts is a major barrier to optimizing care and improving outcomes among patients with PAD. Future prospective studies should examine the impact of community and health policy interventions that mitigate poor food access.
Abstract 15045: Impact of Left Ventricular Assist Device (LVAD) Type on Arrhythmic Outcomes in Patients With Continuous Flow LVADs
Authors: Rakesh Gopinathannair, Dhanunjaya Lakkireddy, Naga Pothineni, Henri Roukoz, Adarsh Bhan, Mustafa Ahmed, Adnan Ahmed, Rishi Charate, Donita Atkins, Deepak Padmanabhan, Sandeep Gautam, Sandeep Gautam, Philip L Mar, Mark S Slaughter, Jaimin Trivedi
Journal: Circulation (2022)

Introduction: Cardiac arrhythmias are common in continuous flow left ventricular assist device (LVAD) recipients. The impact of axial vs. intrapericardial centrifugal LVAD pumps on arrhythmia incidence and associated clinical outcomes is unclear. Hypothesis: This multicenter study evaluated the impact of LVAD type (axial vs. centrifugal) on incidence of atrial and ventricular arrhythmias, ICD shocks and mortality in LVAD patients. Methods: Analysis was done on 536 patients who underwent LVAD implantation at 5 US centers from 2008 to 2016. The groups were divided based on their LVAD type (axial - HeartMate II [HMII, n=433] vs. centrifugal - HeartWare (HW, n=103). Baseline characteristics as well as incidence of post-LVAD atrial arrhythmias (PL-AA), ventricular arrhythmias (PL-VA) and ICD shocks were analyzed in these groups. Multivariable Cox Regression analysis was used to identify predictors of survival. Results: Of 536 patients, 433 had HMII axial LVAD and 103 had HW centrifugal VAD implant. At baseline, HMII group had more males, higher proportion of CRT-D and higher prevalence of AA (Table 1A). Left ventricular dimensions were similar between groups. During a median follow-up of 537 days of LVAD support, incidence of PL-VA and ICD shocks were significantly higher in the HM2 group compared to HW group whereas incidence of PL-AA was not significantly different (Table 1A). In multivariable Cox Regression analysis, LVAD indication was the only variable that predicted survival (Table 1B). Type of LVAD (axial vs. centrifugal) was not associated with survival (HMII vs. HW - HR 1.04, P=0.48). Conclusions: In this multi-center continuous flow LVAD cohort, axial HM2 VAD patients had a higher incidence of PL-VA and ICD shocks. Type of LVAD (axial vs. centrifugal) was not associated with survival.
Abstract 15178: Impact of Anemia on Mortality Among Patients With Type 2 Myocardial Infarction
Authors: Suud Kiradoh, Greg Russell, Steven Greenberg, Brett Schuchardt, Parag A Chevli, Luqman Arafath Thazhathuveetil Kunahamed
Journal: Circulation (2022)

Introduction: Anemia, a common precipitant of Type 2 Myocardial Infarction (T2MI), is well studied in Acute Coronary Syndrome (ACS), but its impact on mortality in T2MI population is lacking. We evaluated the association of hemoglobin (Hgb) levels on all-cause mortality within 60 days in patients with T2MI. Methods: In this single-center retrospective study, we evaluated 812 patients with Hgb &gt; 7g/dl and troponin &gt;0.04 ng/L (&gt;99 th percentile) presenting to a tertiary ED from 08/2016-08/2018. Exclusion criteria included patients with ischemic EKG changes, ACS treatment, cardiac catheterization showing intervenable lesions. Adjusted confounding variables are included in the figure. Iterative code was created to test each possible Hgb cut-off, from 7.1 to 15.2, to maximize the area under the curve while also looking for the smallest p-value and largest odds ratio. Five Hgb categories were then created, and mortality was calculated across groups. A multivariate-adjusted logistic regression model was used to predict mortality using Hgb category 13+ as the reference group. Results: Cut-off analysis showed Hgb of 9.9 as an inflection point of maximal mortality benefit (p&lt;0.0001). Thus, our Hgb categories were 7-9.9, 10-10.9, 11-11.9, 12-12.9, and 13+. 60-day mortality rate for the above respective groups were 45.4% (n=216), 40.0% (n=135), 36.5% (n=104), 34.8% (n=115), and 26.9% (n=242) respectively. The overall 60-day mortality was 36.3% (295/812). In comparison with the reference group, multivariate analysis showing ORs for 60-day mortality for the above Hgb categories were 1.92 (95% CI: 1.28-2.96, p-0.003), 1.42 (0.87-2.32, p-0.16), 1.46 (0.86-2.49, p0.16), and 1.46 (0.88-2.42, p-0.15) respectively. Conclusions: Hospitalized patients with T2MI have an exceptionally high mortality rate that independently correlate with anemia severity. Those with Hgb &lt; 9.9 had significantly higher mortality compared to Hgb &gt; 9.9.
Abstract 14698: Identifying Sources of Prostacyclin Outside the Vascular Wall and Their Contribution to Cardiovascular Protection
Authors: Maria Lopes Pires, Maria Vinokurova, Fisnik Shala, Blerina Ahmetaj-Shala, Paul C Armstrong, Harvey R Herschman, Jane A Mitchell, Nicholas S Kirkby
Journal: Circulation (2022)

Introduction: Prostacyclin is a key anti-thrombotic hormone synthesised through cyclooxygenase (COX) enzymes. Historically, its production has been almost universally associated with the endothelium however the role of non-vascular sources has not been systematically evaluated due to a lack of suitable tools. This has resulted in an underappreciation of its cardiovascular biology and role in other contexts. Hypothesis: We hypothesised that cells outside the vascular wall contribute to generation of prostacyclin which can enter the circulation to provide anti-thrombotic protection. Methods: Global, endothelial and fibroblast COX1 or COX2 knockout mice were studied alongside freshly isolated healthy human lung tissue and primary cell cultures. Prostacyclin levels in plasma and released from cells/tissue ex vivo were measured by ELISA. Individual cell populations were isolated by FACS. Thrombosis in vivo was measured using a FeCl 3 -carotid artery injury model. Results: Vascular endothelial COX1 deletion strongly reduced prostacyclin release from mouse aorta and heart, but not from isolated lung, colon, kidney or spleen (Fig A). This non-vascular prostacyclin required COX1 as it was abolished by global COX1 and not COX2 deletion. Freshly isolated lung fibroblasts exhibited greater prostacyclin synthesis than endothelial or other cell types (Fig B) and this was confirmed in primary human lung cell cultures. Deletion of COX1 from fibroblasts in mice reduced lung prostacyclin release (Fig C) and plasma prostacyclin levels (Fig D) and this was associated with accelerated thrombotic occlusion after carotid artery injury (Fig E). Conclusions: These findings define a new paradigm in prostacyclin biology in which fibroblast/non-vascular-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombosis. This may have particular relevance to understanding how local diseases of the lung result in cardiovascular risk.